Sources of dynamic variability in NF-κB signal transduction: a mechanistic model

Mothes, J.; Busse, D.; Kofahl, B.; Wolf, J.

Sources of dynamic variability in NF-κB signal transduction: a mechanistic model

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Item Type:	Article
Title:	Sources of dynamic variability in NF-κB signal transduction: a mechanistic model
Creators Name:	Mothes, J., Busse, D., Kofahl, B. and Wolf, J.
Abstract:	The transcription factor NF-{kappa}B (p65/p50) plays a central role in the coordination of cellular responses by activating the transcription of numerous target genes. The precise role of the dynamics of NF-{kappa}B signalling in regulating gene expression is still an open question. Here, we show that besides external stimulation intracellular parameters can influence the dynamics of NF-{kappa}B. By applying mathematical modelling and bifurcation analyses, we show that NF-{kappa}B is capable of exhibiting different types of dynamics in response to the same stimulus. We identified the total NF-{kappa}B concentration and the I{kappa}B{alpha} transcription rate constant as two critical parameters that modulate the dynamics and the fold change of NF-{kappa}B. Both parameters might vary as a result of cell-to-cell variability. The regulation of the IκBα transcription rate constant, e.g. by co-factors, provides the possibility of regulating the NF-{kappa}B dynamics by crosstalk.
Keywords:	Bifurcation Analysis, Cell-to-Cell Variability, Fold Change, I{kappa}B{alpha} Transcription, Mathematical Model, Oscillations, Steady State
Source:	BioEssays
ISSN:	0265-9247
Publisher:	Wiley-Blackwell
Volume:	37
Number:	4
Page Range:	452-462
Date:	April 2015
Official Publication:	https://doi.org/10.1002/bies.201400113
PubMed:	View item in PubMed

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